Combined Gold and Photoredox Catalysis: Synthesis of 3-Alkenyl-2H-Indazoles from 2-Alkynylazobenzenes

Clara Mañas, Estíbaliz Merino*

We disclose the intramolecular synthesis of 3-alkenyl-2<i>H</i>-indazoles from 2-alkynylazobenzenes promoted by a dual catalysis using AuCl3 and a ruthenium photocatalyst under irradiation with visible light. This reaction goes through a hydroamination of the alkynyl fragment. The yields are governed by the electronic factors. Control experiments and DFT calculations suggest that a radical and polar mechanisms are operating in parallel. This transformation goes through first formation and C-N bond and 1,2-hydride shift. Derivatization was also carried out to extend the versatility of this methodology.

Adv. Synth. Cat. 2024
DOI: 10.1002/adsc.202400990

Copper-Catalyzed Hydroamination of 2-Alkynylazobenzenes: Synthesis of 3-Alkenyl-2H-Indazole

Clara Mañas, Juan Herrero-Bourdieu, Estíbaliz Merino*

A copper-catalyzed intramolecular synthesis of 3-alkenyl-2H-indazoles from 2-alkynylazobenzenes is described. The reaction proceeds in a single step via C–N bond formation and a subsequent 1,2-hydride shift, affording products in high yields. DFT calculations suggest the 1,2-hydride shift as the rate-determining step. Further derivatization enables functionalization of the 3-alkenyl-2H-indazoles.

J. Org. Chem. 2024.
DOI: 10.1021/acs.joc.4c02144

Shaping cycles with light: a regiodivergent approach to tetracyclic aza-aromatic compounds

Clara Mañas, Ana Belén Ibarra, Estíbaliz Merino*

The development of regiodivergent methods that allow access to different structures from a single substrate through intramolecular processes is crucial for accelerating new molecule discovery, as well as making processes more sustainable and efficient in terms of waste production and economy. In this study, we report a novel regiodivergent cyclization procedure to access two distinct azapolyaromatic regioisomers from 2-alkynylazobenzenes. The key to achieving this regiodivergence lies in the presence or absence of a gold catalyst. The irradiation with visible light of 2-alkynylazobenzenes in the presence of a Ir photocatalyst affords 11H-indolo[1,2-b]indazoles, whereas under similar conditions with AuCl₃, indazolo[2,3-a]quinolines are produced. Control experiments and DFT calculations suggest that both transformations operate through different reaction mechanisms: the formation of 11H-indolo[1,2-b]indazoles involves a radical mechanism, whereas the formation of indazolo[2,3-a]quinolines appears to proceed predominantly through a polar mechanism. This transformation enables the one-step conversion of simple 2-alkynylazobenzenes into diverse azapolyaromatic structures via an intramolecular visible light-promoted process, holding significant potential for new nitrogenated heterocycles.

Org. Chem. Front. 2024.
DOI: 10.1039/d4qo01606h

As every year, the University of Alcalá has celebrated its solemn opening ceremony for the academic year with the traditional procession, from the Cathedral to the Main Hall, of the academic community formed by university professors dressed in academic ropes.

This year, Prof. Patrica García García, Dr. Estíbaliz Merino and Dr. Javier Carreras have attended to the ceremony due to their recent appointment as Full professor and Associate Professors respectively. They have been accompanied by the Emeritus Prof. Juan Jose Vaquero

Congrats!

Selective Synthesis of Boron-Functionalized Indenes and Benzofulvenes by BCl3-Promoted Cyclizations of ortho-Alkynylstyrenes

Marcos Humanes, Ester Sans-Panadés, Cintia Virumbrales, Ana Milián, Roberto Sanz, Patricia García-García*, Manuel A. Fernández-Rodríguez*

Org. Lett. 2024, ASAP
DOI: acs.orglett.4c02092

A selective, metal-free synthesis of boron-functionalized indenes and benzofulvenes via BCl₃-mediated cyclization of o-alkynylstyrenes is described. The method allows precise control over product formation by adjusting reaction conditions. These borylated products were utilized in diverse C–B bond derivatizations and in the total synthesis of Sulindac, a nonsteroidal anti-inflammatory drug, demonstrating the versatility and practicality of the developed methodology for synthetic applications.

X SEQT Young Research Symposium

Madrid (Spain), July 12

Our PhD student Marta Duran has attended to the annual meeting for young researchers organized by the Spanish Society of Medicinal Chemistry

https://sites.google.com/view/seqtxyrs/home?authuser=0

– Flash & Poster:
· Targeting chronic kidney dissease trough new small molecules modulating the pseudokinase Integrin-Linked Kinase
Marta Durán Martínez, Mercedes Griera Merino, Sergio de Frutos García, José Luis Aceña, Laura Calleros, Diego Rodríguez Puyol, Javier García Marín

Balticum Organicum Syntheticum 2024

Riga (Latvia), July 7-10

Our research group has been represented at the Balticum Organicum Syntheticum biennial international conference on organic synthesis.

– Poster:
· Gold-Catalyzed Selective Synthesis of Polycyclic Frameworks Containing Tricyclic Bridgehead Carbon Centres
Manuel A. Fernández-Rodríguez, Lucía Sánchez-Jiménez,Adrián Gargantiel, Patricia García-García

– Poster:
· Metal-Free Borylative Cyclizations of Enynes: Useful Methodologies for the Synthesis of Borylated Polycycles
Ana Milian, Marcos HUmanes, Ester Sans-Panadéz, Manuel A. Fernández-Rodríguez Patricia García-García

XXIX Reunión Bienal de Química Orgánica

Santa Cruz de Tenerife, 26 – 28 June

Last June 26th, the Chemical Biology Group from the university of Alcalá was  well represented in the bienal meeting of the Organic Chemistry Group from the Royal Society of Chemistry.

– Oral:
· A Journey into Unexplored Photoreactivity of Alkynylazobenzenes
Estíbaliz Merino

– Flash + Poster:
· Visible-light-mediated modification of amino acid derivatives
Guillermo Morales-Ortega, Javier Carreras

– Flash + Poster:
· Synthesis of novel 3,4-Dihydroquinazolinones via base promoted [4+2] cycloaditions
Sergio Torres-Oya, Manuel A. Fernández-Rodríguez, Mercedes Zurro

– Flash + Poster:
· Synthesis of borylated carbocycles via metal-free borylativee cyclizations of o-alkynylstyrenes
Marcos Humanes, Patricia Garcia-Garcia, Manuel A. Fernández-Rodríguez

– Flash + Poster:
· An approach to the synthesis of nonproteinogenic amino acid Caramboxin
Jose Antonio García-García, Esther Sans, David Sucunza, Jose Luis Aceña Bonilla, Juan J. Vaquero.

The Chemical Biology group wanted to acknowledge two of their past members, Prof. Julio Álvarez Builla and Dr. Mª Luisa Izquierdo, for their contributions to the group and to the University of Alcalá.

They provided made remarkable contributions to both the group and the University of Alcalá throughout their long and distinguished careers in research and teaching.

Some of their colleagues gathered to celebrate their achievements and express gratitude for their dedication and impact on the academic community and on the Chemical Biology Group.

Thank you Marisa & Julio !

Dra. Rosa Adam talk

Dra. Rosa Adam, “Ramón y Cajal” Researcher at Organic Chemistry Department of the Universidad de Alcalá (Madrid)
Diseño racional de materiales metálicos nanoestructurados como catalizadores para el desarrollo de procesos de síntesis orgánica más sostenibles
Room 0.6, Edificio Polivalente, UAH. Jun 04h, 12.00.